This project has emphasized the characterization of the cocaine binding site in rat striatal membranes. Binding is rapid, saturable, reversible and dependent on tissue concentration. In striatal membranes, sodium induces a two-fold increase in the maximal number of binding sites without altering their affinity for cocaine. This stimulatory effect is specific to sodium, concentration-dependent, and occurs in membranes prepared from striatum but not from other brain regions. Sodium-dependent binding is eliminated following 6-hydroxy-dopamine-induced lesions of the striatum, suggesting that the binding site is localized presynaptically on dopaminergic nerve terminals. This finding in conjunction with experiments determining the ability of various drugs to compete for the cocaine binding site, suggests that the sodium-sensitive binding site is related to dopamine uptake sites in striatum. However, the sodium sensitivity does not appear to be related to the presence of an endogenous inhibitor of cocaine binding, since this factor is present not only in striatum, but also in brain regions not demonstrating sodium-stimulated binding.